Our studies confirm the importance of alternative pathway activation in the expression of skin and kidney organ inflammation in the MRL/lpr lupus-prone mouse. CRIg-Fc limits immunoglobulin and complement deposition, as well as the presence of macrophages and other inflammatory cells in the kidney without affecting the levels of serum anti-DNA antibodies. Furthermore, CRIg-Fc suppresses skin inflammation. Though the important contribution of the AP to lupus pathogenesis has been recognized in lupus-prone mice, the apparent non-contribution of the classical pathway to the expression of organ damage in the MRL/lpr mouse is intriguing and unexpected. We propose that CRIg-Fc and other inhibitors of the alternative complement pathway such as anti-factor B antibodies [17] should be considered for the treatment of patients with SLE.